EU/3/09/616

Orphan designation

On 27 February 2009, orphan designation (EU/3/09/616) was granted by the European Commission to Knopp Neurosciences Sub Ltd, United Kingdom, for (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydrochloride monohydrate for the treatment of amyotrophic lateral sclerosis.

The sponsorship was transferred to Biogen Idec Limited, United Kingdom, in March 2011.

Amyotrophic lateral sclerosis is a progressive disease of the nervous system, where the nerve cells in the brain and spinal cord that control voluntary movement gradually deteriorate. This causes the muscles under their control to weaken and waste away, leading to paralysis. Symptoms of amyotrophic lateral sclerosis vary from patient to patient, depending on which muscles weaken first, and include tripping and falling, loss of control of the hand and arm movement, difficulty in speaking, swallowing and breathing, persistent tiredness, and twitching and cramping. Amyotrophic lateral sclerosis usually starts in mid-life. Men are about one-and-a-half times more likely to have the disease than women.
Amyotrophic lateral sclerosis is a debilitating and life-threatening disease because it also affects the muscles that are used to breathe.

At the time of designation, amyotrophic lateral sclerosis affected approximately 0.8 in 10,000 people in the European Union (EU)*. This is below the threshold for orphan designation, which is 5 in 10,000, and is equivalent to around 40,000 people. This is based on the information provided by the sponsor and previous knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 504,800,000 (Eurostat 2009).

At the time of designation, there was one medicine called riluzole authorised for amyotrophic lateral sclerosis in the EU.

The sponsor has provided sufficient information to show that (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydrochloride monohydrate might be of significant benefit for the treatment of amyotrophic lateral sclerosis because it might improve treatment of patients with this condition. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

(6R)-4, 5, 6, 7-tetrahydro-N6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate acts on the nervous system. The exact way in which it will work in amyotrophic lateral sclerosis is not known. It is expected to prevent nerve cells from deteriorating by reducing the production of ‘reactive oxygen species’ (ROS, toxic molecules containing oxygen) that damage nerve cells and of other messenger substances that stimulate cell death.

This medicine is the ‘enantiomer’ of pramipexole, a medicine approved in the EU for the treatment of Parkinson’s disease and restless legs syndrome. This means that this medicine has the same chemical formula, but a different shape: it is the mirror image of pramipexole. However, it is not expected to work in the same way as pramipexole in the body.

The effects of (6R)-4, 5, 6, 7-tetrahydro-N6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with amyotrophic lateral sclerosis were ongoing.

At the time of submission, (6S)-4, 5, 6, 7-tetrahydro-N6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate (pramipexole) was authorised in the EU for the treatment of Parkinson’s disease and restless legs syndrome. Orphan designation of (6R)-4, 5, 6, 7-tetrahydro-N6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate had been granted in the United States of America for amyotrophic lateral sclerosis.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 January 2009 recommending the granting of this designation.

he existence of alternative methods of diagnosis, prevention or treatment;

either the rarity of the condition (affecting not more than 5 in 10,000 people in the Community) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.